The cellular and molecular mechanisms that underlie alcohol's behavioral effects have not been established. This project studied the effect of ethanol on synaptic mechanisms using the whole-cell patch-clamp technique. Ethanol inhibited ion current activated by the glutamate agonist NMDA in a concentration-dependent manner over the concentration range 5 to 50 mM, a range that produces intoxication. The inhibition was not voltage- or use-dependent, was not due to an alteration of the ion selectivity of the ionophore and did not appear to involve an interaction with a regulatory site on the channel. The inhibition was correlated with the hydrophobicity of different alcohols suggesting a novel interaction with hydrophobic region of the NMDA channel. The inhibition was also correlated with the intoxicating potency of different alcohols, suggesting that the inhibition may contribute to the cognitive and neural impairments associated with intoxication. Ethanol inhibited kainate- and quisqualate-activated current in a concentration- dependent manner over the concentration range 50 to 200 mM, a range that produces general anesthesia. GABA-A activated ion current was potentiated by ethanol in some neurons and not affected by ethanol in other neurons. The concentration that potentiated GABA-A activated current was 10 to 50 mM. GABA-A current was also potentiated by benzodiazepines, suggesting that the augmentation of this current by ethanol may contribute to the anxiolytic actions of ethanol. Intoxicating concentrations of ethanol were also found to potentiate the ion current mediated by activation of the 5-HT-3 type of serotonin receptor. Behavioral experiments suggest that this effect may be associated with the recognition of ethanol action. Ethanol also produced a concentration-dependent inhibition of the ion current associated with ATP-gated ion channels over the concentration range 6 to 250 mM. The observations suggest that neurotransmitter-gated ion channels may be molecular sites of ethanol action in the CNS. In addition, the behavioral effects of ethanol may result from actions of ethanol on these receptor-gated channels.